This NIMH Mentored Quantitative Research Development Award (K25) application will support Dr. Wen-Jang Chu's long-term career goal of developing expertise in applying advanced magnetic resonance spectroscopy (MRS) and imaging (MRI) methods to study the neuropathology of psychiatric illness. The scientific goal of this proposal is to differentiate the neuropathology of bipolar disorder and schizophrenia using functional MRI (fMRI) -guided MRS. The candidate's previous scientific background is in MRS method development and its application on high-field MR systems (>3Tesla) but lacks the clinical research experience in psychiatric disorders to conduct independent research in this field. In order to complement the candidate's long-term research career goal, this proposal emphasizes clinically related trainings to allow him to obtain sufficient experience in this 3-year award. The candidate will effectively integrate his previous MRI and MRS experience with clinically related research experience with guidance from the mentors. This proposal extends the applicant's previous MRS background into the study of psychiatric illness using the excellent training environments of a clinically-oriented MRI research center and outstanding bipolar and schizophrenia research mentorship at the University of Cincinnati. The research portion of this proposal investigates 1) the dysfunction of glutamatergic neurotransmission in bipolar disorder and schizophrenia using modified TE-averaged single- voxel MRS method, and 2) abnormal brain activation in patients using fMRI. The integration of MRI, MRS and cognitive and behavior measures in this protocol provides a comprehensive approach to the study of these two mental disorders and also allows candidate to develop new MR techniques and research methods for psychiatric illness research. The main goal of this 3-year K-25 award is to provide the candidate with sufficient training so that he can submit NIH RO1 grant proposals at the end of project, which will promote his future independent research in psychiatric illness. PUBLIC HEALTH RELEVANCE: Bipolar disorder and schizophrenia are the 6th and 9th leading causes of disability worldwide. These two psychiatric disorders share considerable symptom and treatment overlap. This proposed work will not only help improve therapy by clarifying the link between neurotransmitters and brain activation in bipolar disorder and schizophrenia but also provides new research protocols for psychiatric disorders using advanced MR methods and cognitive neuroscience.